This study will characterize trends in incidence of HIV, HCV and OD associated with binational drug markets and drug tourism (DT) between San Diego (SD) and Tijuana (TJ), Mexico. TJ sits on a major drug trafficking route whereby heroin, fentanyl, meth & cocaine are trafficked to the US. After Mexico partially decriminalized small amounts of drugs in 2009, 1 in 6 people who inject drugs (PWID) in SD reported injecting drugs in TJ, where drugs were ?cheaper and easier to buy?. Since Mexico recently relaxed its opiate prescription laws, disparities in drug availability and price between SD and TJ will likely widen, fueling increased DT that will impact the above health outcomes. We hypothesize that greater penetration of fentanyl into local drug markets will be associated with riskier behaviors that increase HIV and HCV incidence. Our study is timely since retail drug markets are changing in Tijuana with drug tourists likely to be acquiring riskier behaviors. Health outcomes in these border cities likely serve as a ?bellwether? for other U.S. cities. The specific aims for our proposed study, called La Lnea (?The Line?) are: AIM 1. To prospectively characterize cross-border DT between SD and TJ and its association with retail drug market characteristics. AIM 2. To characterize retail drug market trends in TJ versus SD by conducting epidemiologic and ethnographic surveillance, triangulating quantitative and qualitative findings and DEA administrative data. AIM 3. To study real-time HCV and HIV cross-border transmission among PWID with molecular epidemiology. AIM 4. To characterize OD incidence and its associations with drug retail markets and DT. AIM 5. To conduct dynamic modeling of future HIV, HCV and OD incidence among PWID in SD in the context of changing drug retail markets to inform prevention interventions. La Lnea will conduct prospective quantitative and qualitative surveillance of retail drug markets in both SD and TJ, coupled with epidemiologic data collection of 600 PWID (200 drug tourists from SD; 200 non-drug tourists from SD and 200 non-drug tourists from TJ) and an ethnographic sub-cohort (N=75; 25 per group). We will analyze PWIDs? HIV and HCV sequencing data to prospectively assess cross-border transmission. We will incorporate longitudinal data on binational retail drug markets and HIV and HCV sequencing data into dynamic mathematical models to forecast future HIV, HCV and OD incidence trends. Since the direction of cross-border HIV transmission is now occurring from Mexico to the US for the first time and HIV incidence among PWID in TJ is high, monitoring trends in HIV and HCV incidence in the border region is critical to avoid future US outbreaks. This study addresses both the NIDA?s HEAL initiative and the Trans-NIH plan of the OAR, by conducting time-sensitive research to inform implementation of timely interventions to reduce incidence of HIV, HCV and OD.